Cancer treatment courses which rely on imaging and spatially-dependent therapy involve making multiple treatment decisions (e.g., radiotherapy alone, radiotherapy plus chemotherapy, induction chemotherapy) over time. These decisions depend on complex factors, including the tumor location with respect to sensitive organs and its response to treatment, laboratory data, toxicity, anticipated side effects and survival probability. In this project, we design and develop novel statistical methodology for dynamic and personalized treatment decisions with specific application to head and neck cancer radiotherapy planning. The empirically-derived treatment rules developed in this project have the potential to improve the standard of care (i.e., treatment plans chosen by the tumor treatment board) and the quality of life of surviving patients. The methods developed in the proposal may be used to derive optimal treatment strategies across not only a variety of spatially-dependent cancer diagnoses, but also other chronic conditions including mental health disorders, substance abuse diseases, or diabetes, that require making multiple decisions that must weigh the tradeoffs between efficacy and toxicity. This Big Data collaboration effectively bridges the quantitative sciences with biomedicine, and provides quantitative techniques for leveraging the largest existing repository of head and neck cancer data in the country.